Associations Between Homeostasis Model Assessment (HOMA) and Routinely Examined Parameters in Individuals With Metabolic Syndrome.

The aim of the study was to investigate whether routine clinical parameters, including visceral adiposity index (VAI) and atherogenic index of plasma (AIP), could become widely applicable predictors of insulin resistance (IR), evaluated using homeostasis model assessment (HOMA-IR, HOMA-ß), with regard to presence of metabolic syndrome (MS). The study comprised 188 individuals identified to meet the MS criteria during regular health examinations and an equal number of age, sex-matched controls without MS. The strongest correlations were noted between HOMA-IR and waist circumference (WC) in the MS group (r=0.57) as well as between HOMA-IR and alanine aminotransferase (ALT, r=0.57) or aspartate aminotransferase (r=0.56) in the controls, with a statistical significance of p<0.001. In a multivariate linear regression model, the predictors of HOMA-IR were WC (linear coefficient ß=0.1, p<0.001), ALT (ß=2.28, p<0.001) and systolic blood pressure (ß=0.04, p<0.001). HOMA-ß was determined by WC (ß=1.97, p=0.032) and ALT (ß=99.49, p=0.004) and inversely associated with age (ß=-1.31, p=0.004). Neither VAI nor AIP were significant predictors. The presence of MS was significantly associated with both HOMA-IR and HOMA-ß. These results indicate that WC and ALT appear to be reliable predictors of IR. Comprehensive assessment of these parameters may serve for estimating the level of IR.

Superior Role of Waist Circumference to Body-Mass Index in the Prediction of Cardiometabolic Risk in Dyslipidemic Patients.

Coronary risk evaluation by conventional factors (age, gender, smoking, blood pressure and cholesterol) may further be specified by facets of the metabolic syndrome, namely insulin resistance, hypertriglyceridemia and obesity. Although obesity is usually defined as elevated body mass index (BMI), recent data indicate a superior role of waist circumference or hypertri-glyceridemic waist (HTGW) over BMI in the assessment of cardiometabolic risk. In dyslipidemic patients, the specific contributions of risky waist, HTGW or BMI have not been evaluated as yet. 686 dyslipidemic subjects (322 males and 364 females) were enrolled into a cross-sectional study. In each subject basic antropometry (i.e. waist circumference, HTGW, BMI) and laboratory parameters of lipid profile and insulin resistance were determined. Cardiometabolic risk was given by fulfilling the criteria (harmonized definition) of metabolic syndrome. The significance of risky waist, HTGW and BMI were assessed by comparing the respective predictive values for the presence of metabolic syndrome. Dyslipidemic patients with risky waist, HTGW or high BMI have a more atherogenic lipid profile and higher insulin resistance compared to those without risky waist, HTGW or high BMI. Risky waist is stronger predictor of metabolic syndrome (PPV 66 %, NPV 90 %) and thus posesa greater cardiometabolic risk than higher BMI per se does (PPV 42 %, NPV 97 %). The contribution of triglycerides (i.e. HTGW) to these predictive values is marginal (PPV 66 %, NPV 92 %). The present results highlight the superior role of waist circumference as a screening tool over BMI for the evaluation of cardiometabolic risk in dyslipidemic subjects. HTGW brings little additional benefit in risk stratification. Lower BMI proved to be optimal for identifying the subjects with inferior risk.

Inverse association of lipoprotein (a) with markers of insulin resistance in dyslipidemic subjects.

Lipoprotein (a) [Lp(a)] is an LDL-like particle that contains an apolipoprotein B100 molecule covalently bound to a plasminogen-like glycoprotein, apolipoprotein (a) [apo(a)]. Epidemiological evidence supports a direct and causal association between Lp(a) levels and coronary risk. On the contrary, a few prospective findings demonstrate inverse association of Lp(a) levels with risk of type 2 diabetes (T2DM). The aim of our study was to evaluate the association of Lp(a) with indicators of insulin resistance (IR) and metabolic syndrome (MS), which precede development of T2DM. We enrolled 607 asymptomatic dyslipidemic subjects (295 men and 312 women, mean age 45.6+/-14.0 years) into our cross-sectional study. Lp(a) concentrations correlated inversely with TG, AIP, insulin, HOMA, C-peptide, BMI, waist circumference, and number of MS components (p<0.01 for all). Subjects with MS had significantly lower Lp(a) concentrations in comparison with those without the presence of this phenotype (p<0.0001). Serum concentrations of Lp(a) in the lower (1(th)-3(rd)) quartiles of insulin and HOMA were significantly higher than in the 4(th) quartile of these insulin resistance markers (p<0.001). Odds ratios of having increased markers of IR (TG, HOMA) and MS in top quartile of Lp(a) also indicate inverse association of Lp(a) with IR. The results of our study support an inverse association of Lp(a) levels with IR and MS that precedes overt T2DM diagnosis.

Correlation of uric acid levels and parameters of metabolic syndrome.

Hyperuricemia has been described as associated with the risk of development metabolic syndrome; however the relationship between the uric acid level and particular parameters of metabolic syndrome remained unclear. We performed a cross-sectional study on a cohort of 833 dyslipidemic patients and correlated their levels of uric acid with parameters of insulin resistance, lipid metabolism, C-reactive protein, anthropometric parameters. We also defined patients with hypertriglyceridemic waist phenotype and compered their uric acid levels with those without this phenotype. We found that levels of uric acid are associated with parameters of metabolic syndrome. Specifically, dyslipidemia characteristic for metabolic syndrome (low HDL-cholesterol and high triglycerides) correlates better with uric acid levels than parameters of insulin resistance. Also waist circumference correlates better with uric acid levels than body mass index. Patients with hypertriglyceridemic waist phenotype had higher levels of uric acid when compared with patients without this phenotype. Serum uric acid levels are even in low levels linearly correlated with parameters of metabolic syndrome (better with typical lipid characteristics than with parameters of insulin resistance) and could be associated with higher cardiovascular risk.

Hypertriglyceridemic waist - a simple clinical tool to detect cardiometabolic risk: comparison with harmonized definition of metabolic syndrome.

With the increasing prevalence of obesity and especially abdominal obesity, a simple clinical tool is needed that identifies the cardiometabolic risk for cardiovascular disease and type 2 diabetes. The aim of our study was to evaluate a broad spectrum of metabolic variables and IMT in subjects with and without hypertriglyceridemic waist (HTGW) and compare it with the harmonized definition of metabolic syndrome (MS) with both a higher (MS-I) and lower waist circumference (MS-II) for Europids. We enrolled 607 asymptomatic dyslipidemic subjects (295 men and 312 women) into our cross-sectional study. The subjects with HTGW had an atherogenic lipid profile (significantly higher triglycerides, AIP, non-HDL-C, lower HDL-C and ApoA-1, and the women also higher TC and ApoB), increased markers of insulin resistance (insulin, HOMA, C-peptide, proinsulin), inflammation (hsCRP), thrombosis (fibrinogen, PAI-1), SBP and DBP, and lower adiponectin (p<0.05-0.001 for all). These risk factors were entirely similar in HTGW, MS-I and MS-II. Age-adjusted IMT was significantly higher only in the women with HTGW but this significance disappeared after further adjustment for TC, SBP, and smoking. Our results support the routine use of HTGW as a simple and inexpensive screening tool to detect subjects at increased cardiometabolic risk in clinical practice.

Correlation of lipid parameters and markers of insulin resistance: does smoking make a difference?

Insulin resistance associated with dyslipidemia enhances cardiovascular risk. Several atherogenic indexes have been suggested to give more precise information about the risk. The aim of our study was to estimate, which atherogenic index correlates better with parameters of insulin resistance. Furthermore, we compared the parameters of lipid metabolism and insulin resistance between smokers and non-smokers. In our cross-sectional study we enrolled 729 patients with dyslipidemia which were divided into two groups - non-smokers (586) and smokers (143). We measured lipid profile, parameters of insulin resistance (fasting glycemia, insulin, HOMA-IR, C-peptide, proinsulin) and calculated atherogenic indexes - atherogenic index of plasma (log (TAG/HDL-C), AIP), ApoB/ApoA1 index and nonHDL-C. AIP was found out to show stronger correlations with parameters of insulin resistance (p<0.001, correlation coefficients ranging between 0.457 and 0.243) than other indexes (ApoB/ApoA1 or nonHDL cholesterol). AIP correlated with parameters of insulin resistance both in smokers and non-smokers, but after adjustment (for age, body mass index, waist circumference) persisting only in non-smokers. Smokers had a wider waist circumference and a proatherogenic lipid profile. Smoking increases the risk of developing metabolic syndrome. AIP can be used in daily praxis for predicting insulin resistance in patients with dyslipidemia, predominantly in non-smokers.

Evaluation of total adiponectin, adipocyte fatty acid binding protein and fibroblast growth factor 21 levels in individuals with metabolic syndrome.

Although many studies have investigated the relationships of several adipokines to metabolic syndrome (MetS), the interrelationships of adiponectin (ADP), adipocyte fatty acid binding protein (A-FABP) and fibroblast growth factor 21 (FGF 21) have not been described in detail. We examined 209 asymptomatic dyslipidemic patients divided into MetS+ (n=73) and MetS- (n=136) groups. The aim of study was to evaluate the relationships between observed adipokines, to compare the levels of total ADP, A-FABP and FGF 21 in individuals with and without MetS, and to elucidate the relationships of individual adipokines to lipid parameters, markers of insulin resistance and endothelial hemostatic markers in these groups. In MetS+ group, we found the independent positive association ADP with A-FABP (beta=0.4888, p=0.0382), A-FABP with FGF 21 (beta=0.3811, p=0.0002) and von Willebrand factor (beta=0.4502, p=0.0013), and FGF 21 with A-FABP (beta=0.4422, p=0.0002). Our study has confirmed the well-established risk profile of subjects with MetS, although clinically asymptomatic. MetS+ patients had also lower levels of ADP and higher levels of A-FABP and FGF 21. Our study evaluated the interrelationships of ADP, A-FABP and FGF 21 in asymptomatic dyslipidemic subjects with diagnosis of MetS. Especially strong association between A-FABP and FGF 21 needs to be clarified in further studies.

[Opinion of the Czech Atherosclerosis Society's committee (CSAT) on the ESC/EAS guidelines related to the diagnostics and treatment of dyslipidemias issued in 2011]. / Stanovisko výboru CSAT k doporucením ESC/EAS pro diagnostiku a lécbu dyslipidemií z roku 2011.

This position statement of the Executive Committee of the Czech Society for Atherosclerosis (CSAT) summarizes the most important aspects and novelties of the latest European guidelines for the management of dyslipidemia. In particular the position statement comments on: cardiovascular risk stratification, indications for plasma lipid and lipoprotein levels assessment as well as target lipid values, evaluation of current options for both lifestyle and pharmacological treatment of lipid metabolism disorders and, also, recommendation for laboratory monitoring of patients treated with lipid lowering agents. The statement deals with actual concepts of management of dyslipiemia in everyday practice, e.g. therapy of dyslipidemia in special patients´ groups. This statement does not replace the latest guidelines but focuses on the changes from the former guidelines for dyslipidemia management, published by CSAT in 2007.

Soluble intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 in asymptomatic dyslipidemic subjects.

AIM: The plasma levels of soluble intercellular cell adhesion molecule-1 (s-ICAM-1) and soluble vascular cell adhesion molecule-1 (s-VCAM-1) were assessed in clinically asymptomatic subjects to compare them between normolipidemic and various dyslipidemic phenotypes. The associations between soluble cell adhesion molecules (s-CAMs) and risk factors for atherosclerosis, markers of insulin resistance, and the intima-media thickness of the common carotid artery (IMT) were evaluated, too. METHODS: Thwo hundred and thirty-four asymptomatic subjects were divided into four dyslipidemic phenotypes (DLP) according to apolipoprotein B (apoB) and triglycerides (TG): DLP1 (N.=58, apoB<1.2 g/L and TG<1.5 mmol/L), DLP2 (N.=47, apoB<1.2 g/L and TG≥1.5 mmol/L), DLP3 (N.=31, apoB≥1.2 g/L and TG<1.5 mmol/L) and DLP4 (N.=98, apoB≥1.2 g/L and TG≥1.5 mmol/L). DLP1 (normo-apoB /normo-TG) served as a control group. RESULTS: A significant difference in s-ICAM-1 between DLP1 (502.0 [457.1-568.2] ng/mL) and DLP4 (567.9 [502.8-692.1] ng/mL, P<0.001) was found. No significant differences in s-VCAM-1 between DLPs were apparent. S-ICAM-1 was independently predicted by HDL-cholesterol, non-HDL-cholesterol, proinsulin, C-peptide, waist, systolic and diastolic blood pressure. S-VCAM-1 was predicted only by age and systolic blood pressure. Both s-CAMs were detected as independent predictors for IMT, which was significantly increased in DLP 4. CONCLUSION: The elevation of s-ICAM-1 was presented only in patients with simultaneously elevated TG and apoB (DLP4) in comparison with normolipidemic subjects. Patients with DLP 4 had significantly increased IMT, which was independently predicted by levels of s-ICAM-1 and of s-VCAM-1. These findings pointed out DLP4 subjects as individuals with the highest risk for early manifestation of atherosclerosis.

Lipid-altering efficacy of ezetimibe/simvastatin 10/20 mg compared with rosuvastatin 10 mg in high-risk hypercholesterolaemic patients inadequately controlled with prior statin monotherapy - The IN-CROSS study.

AIMS: To evaluate the efficacy of switching from a previous statin monotherapy to ezetimibe/simvastatin (EZE/SIMVA) 10/20 mg vs. rosuvastatin (ROSUVA) 10 mg. METHODS: In this randomised, double-blind study, 618 patients with documented hypercholesterolaemia [low-density lipoprotein cholesterol (LDL-C) > or = 2.59 and < or = 4.92 mmol/l] and with high cardiovascular risk who were taking a stable daily dose of one of several statin medications for > or = 6 weeks prior to the study randomisation visit entered a 6-week open-label stabilisation/screening period during which they continued to receive their prestudy statin dose. Following stratification by study site and statin dose/potency, patients were randomised to EZE/SIMVA 10/20 mg (n = 314) or ROSUVA 10 mg (n = 304) for 6 weeks. RESULTS: EZE/SIMVA produced greater reductions in LDL-C (-27.7% vs. -16.9%; p < or = 0.001), total cholesterol (-17.5% vs. -10.3%; p < or = 0.001), non-high-density lipoprotein cholesterol (HDL-C) (-23.4% vs. -14.0%; p < or = 0.001) and apolipoprotein B (-17.9% vs. -9.8%; p < or = 0.001) compared with ROSUVA, while both treatments were equally effective at increasing HDL-C (2.1% vs. 3.0%; p = 0.433). More patients achieved LDL-C levels < 2.59 mmol/l (73% vs. 56%), < 2.00 mmol/l (38% vs. 19%) and < 1.81 mmol/l (25% vs. 11%) with EZE/SIMVA than ROSUVA (p < or = 0.001). A borderline significantly greater reduction in triglycerides (p = 0.056) was observed for EZE/SIMVA (-11.0%) vs. ROSUVA (-5.3%). There were no between-group differences in the incidences of adverse events or liver transaminase and creatine kinase elevations. CONCLUSION: EZE/SIMVA 10/20 mg produced greater improvements in LDL-C, total cholesterol, non-HDL-C and apoB with a similar safety profile as for ROSUVA 10 mg.

Relationship between familial combined hyperlipidemia and insulin resistance.

BACKGROUND AND AIMS: Familial combined hyperlipidemia is the most frequent hereditary dyslipidemia, usually associated with insulin resistance. Recently, the diagnostic criteria offamilial combined hyperlipidemia were redefined: There should be at least two 1st degree hyperlipidemic relatives with both triglycerides > or = 1.5 mmol x L(-1) and apolipoprotein B > or = 1.20 g L(-1). The aim of this study was to evaluate the relationship between this lipoprotein phenotype and the presence of insulin resistance and to assess the presence of metabolic syndrome. METHODS: Lipid parameters and parameters associated with insulin resistance were determined in 90 subjects of families with familial combined hyperlipidemia and 38 controls. The members of affected families were further divided into the hyperlipidemic and normolipidemic group. RESULTS: The hyperlipidemic group showed only significantly higher fasting proinsulin levels [HL 17,4 +/- 1.5 vs NL 12.8 +/- 1.4 (p = 0.030); and vs CO 11.1 +/- 1.4 (p = 0.003)] in comparison with the normolipidemic and control groups. Differences in fasting insulin [HL 9.40 +/- 0.78 vs NL 7.78 +/- 0.71 (p = NS); and vs CO 7.30 +/- 0.76 (p = NS)], C-peptide [HL 2.56 +/- 0.19 vs NL 2.27 +/- 0.17 (p = NS); and vs CO 2.07 +/- 0.18 (p = NS)], and HOMA [HL 2.16 +/- 0.21 vs NL 1.84 +/- 0.20 (p = NS); and vs CO 1.69 +/- 0.21 (p = NS)] did not reach statistical significance. On the contrary, the members of families with familial combined hyperlipidemia with the presence of metabolic syndrome (NCEP-ATP III) had significantly higher fasting insulin [FCH with MS 12.74 +/- 1.42 vs HL without MS 9.21 +/- 0.92 (p = 0.030); and vs NL without MS 6.75 +/- 0.80 (p = 0.001)], and proinsulin levels [FCH with MS 25.28 vs HL without MS 15.69 +/- 1.75 (p = 0.002); and vs NL without MS 11.20 +/- 1.51 (p = 0.0001)], and HOMA index [FCH with MS 3.03 +/- 0.39 vs HL without MS 2.13 +/- 0.25 (p = 0.042); and vs. NL without MS 1.56 +/- 0.22 (p = 0.003)] in comparison with their relatives without metabolic syndrome and controls. CONCLUSION: The presence of the metabolic syndrome could detect the most insulin resistant subjects in families with familial combined hyperlipidemia who are at increased risk of cardiovascular disease.

[Czech atherosclerosis society guidelines for the diagnosis and treatment of dyslipidemia in adults]. / Doporucení pro diagnostiku a lécbu dyslipidémií v dospelosti, vypracované výborem Ceské spolecnosti pro aterosklerózu.

The present guidelines are based on the recommendations published in 2005 entitled "Prevention of Cardiovascular Diseases in Adulthood" summarizing the conclusions of nine Czech medical societies and agree with them in the assessment of individual risk of mortality from cardiovascular disease (CVD) according to SCORE tables. They reflect new research data in pathophysiology of dyslipidemias (DLP) and particularly the results of recent clinical trials of lipid-lowering therapy and their meta-analyses. They establish priorities for the screening and management of DLP, present suitable diagnostic methods, additional investigations of potential use in risk assessment, including some emerging risk factors and detection of sub-clinical atherosclerosis in persons in a moderate-risk category. Major changes include a lower LDL-cholesterol treatment target (< 2.0 mmol/L for all CVD individuals) and a possible use of apolipoprotein B as a secondary target in selected persons (< 0.9 g/L in high risk without CVD, < 0.8 g/L for CVD patients) and nonHDL-cholesterol (< 3.3 mmol/L in high risk without CVD, < 2.8 mmol/L for CVD patients). Therapy of individual DLP phenotypes (monotherapy and combination therapy) as well as basic principles for control examination at lipid-lowering medication are described. Recommended therapeutic lifestyle changes are shown. Enclosed are five annexes: DLP diagnosis; causes of secondary DLP; additional investiga- tions of potential use in risk stratification; familial hypercholesterolemia; list of recommended foods; two variants of SCORE tables for risk assessment for the Czech Republic; the scheme of recommended procedures and treatment algorithm in DLP asymptomatic individuals.

[Dual inhibition of cholesterol using the drug combination ezetimibe/simvastatin?]. / Duální inhibice cholesterolu prostrednictvím prípravku ezetimib/simavastatin (Inegy)--nejsnadnejsí cesta k dosazení cílových hodnot LDL-cholesterolu?

The latest clinical intervention studies of statins have shown that more aggressive reductions in LDL-cholesterol to values lower than existing target values for persons with a high risk of cardiovascular disease produce greater success in terms of halted progression and even regression of the atherosclerotic process and fewer cardiovascular events. This has lead to a series of international and national recommendations for a further reduction in target values for LDL-cholesterol, which is often difficult to achieve with the usual dosage of statins. The combination of a statin with ezetimibe, acting as a dual inhibition mechanism against the synthesis and absorption of cholesterol, reduces LDL-cholesterol significantly more than treatment with a statin in monotherapy. This allows many more patients to achieve the target value for LDL-cholesterol. At present a drug combination comprising ezetimibe 10 mg and simvastatin in all doses (10, 20, 40 and 80 mg) is being introduced into our market under the company name Inegy. In addition to reducing LDL-cholesterol by up to 61% this combination has a positive effect on a range of other parameters for lipid metabolism and inflamation. A typical initial dose of ezetimibe 10 mg/simvastatin 20 mg reduces LDL-cholesterol by around 50%, which is necessary for the stabilisation of atherosclerotic plaque. For patients requiring more aggressive reduction of LDL-cholesterol it is best to start with a dose of ezetimibe 10 mg/simvastatin 40 mg. The highest dose of 10 mg/80 mg is intended for patients with the highest level of risk and reduces LDL-cholesterol by around 60%. In all the studies that have been carried out so far, the combination of ezetimibe and statin was very well tolerated and the safety profile of this combination was the same a treatment with the statin alone. At present a wide range of large clinical studies are underway to test whether LDL-cholesterol reduction using the ezetimibe + statin combination will also lead to a lower risk of cardiovascular events.

[Czech Atherosclerosis Society Guidelines for the diagnosis and treatment of dyslipidemias in adults]. / Doporulení pro diagnostiku a lécbu dyslipidemlí v dospelosti, vypracované výborem Ceské spolecnosti pro aterosklerózu.

The present guidelines are based on the recommendations published in 2005 entitled "Prevention of Cardiovascular Diseases in Adulthood" summarizing the conclusions of nine Czech medical societies and agree with them in the assessment of individual risks of mortality from cardiovascular disease (CVD) according to SCORE tables. They reflect new research data in pathophysiology of dyslipidemias (DLP) and particularly the results of recent clinical trials of lipid-lowering therapy and their meta-analyses. They establish priorities for the screening and management of DLP, present suitable diagnostic methods, additional investigations of potential use in risk assessment, including some emerging risk factors and detection of sub-clinical atherosclerosis in persons in a moderate-risk category. Major changes include a lower LDL-cholesterol treatment target (< 2.0 mmol/L for all CVD individuals) and a possible use of apolipoprotein B as a secondary target in selected persons (< 0.9 g/L in high risk without CVD, < 0.8 g/L for CVD patients) and nonHDL-cholesterol (< 3.3 mmol/L in high risk without CVD, < 2.8 mmol/L for CVD patients). Therapy of individual DLP phenotypes (monotherapy and combination therapy) as well as basic principles for control examination at lipid-lowering medication are described. Recommended therapeutic lifestyle changes are shown. Enclosed are five annexes: DLP diagnosis; causes of secondary DLP; additional investigations of potential use in risk stratification; familial hypercholesterolemia; list of recommended foods; two variants of SCORE tables for risk assessment for the Czech Republic; the scheme of recommended procedures and treatment algorithm in DLP asymptomatic individuals.

Brachial endothelial function in subjects with familial combined hyperlipidemia and its relationships to carotid artery intima-media thickness.

AIM: The aim of this study was to quantify the flow-mediated dilatation (FMD) of brachial artery in asymptomatic members of families with familial combined hyperlipidemia (FCH) and to determine the relation between FMD and risk factors accompanying FCH. We also investigated the association between FMD and the intima-media thickness (IMT) of the common carotid artery. METHODS: Eighty-two members of 29 FCH families were divided into two groups: probands and hyperlipidemic first-degree relatives (HL) (n=47) and normolipidemic first-degree relatives (NL) (n=35). The control (C) groups, C-HL (n=20) and C-NL (n=20), consisted of sex- and age-matched healthy individuals. FMD was assessed in the brachial artery by measuring the change in brachial artery diameter in response to reactive hyperemia. RESULTS: Both hyperlipidemic subjects and their NL had significantly lower FMD (3.4+/-3% vs 6.3+/-2.8%, P<0.001, 5.2+/-2.3% vs 7.8+/-2.8%, P<0.01, respectively) compared to controls. In multivariate backward stepwise regression analysis, FMD in members of FCH families was independently associated with sex (P<0.001), age (P<0.01), C-peptide (P<0.05) and borderline with glycemia (P=0.052). FMD correlated inversely with IMT in all subjects of FCH families and in hyperlipidemic members. In multivariate backward stepwise regression analysis this relation remained independent (P<0.001, P<0.01, respectively). CONCLUSIONS: Members of FCH families showed impaired FMD, which was independently associated with markers of insulin resistance. FMD and IMT were independently associated in hyperlipidemic, but not in normolipidemic members of FCH families.

Detection of early atherosclerosis using the ultrasound parameter of the intima-media thickness of the common carotid artery in families with familial combined hyperlipidemia.

AIM: The aim of the present study was to quantify intima-media thickness (IMT) of the common carotid artery (CCA) in clinically asymptomatic members of familial combined hyperlipidemia (FCHL) families and to evaluate its association with lipids, apoproteins, blood pressure, surrogate markers of insulin resistance, fibrinogen and hs-CRP. METHODS: The group under study consisted of 82 individuals from 29 FCHL families (47 hyperlipidemic [HL] and 35 normolipidemic [NL]). They were compared with the age and sex adjusted control groups of healthy subjects (HL-c, n=20 and NL-c, n=20). IMT was measured by ultrasound at a far wall of both common carotid arteries. RESULTS: Hyperlipidemic subjects had increased IMT compared with healthy controls (0.695+/-0.118 vs 0.599+/-0.074 mm), with an age and sex corrected difference of 86 mm (p<0.001). No difference in IMT was recorded in NL FCHL members in comparison with their healthy controls. In HL subjects, significantly positive univariate correlations were observed between IMT and age, total cholesterol, LDL-cholesterol, non-HDL-cholesterol, apolipoprotein B, SBP, DBP, BMI, waist, fasting glycemia, C-peptide and proinsulin, whereas in NL subjects IMT correlated only with age. Multivariate regression analysis in FCHL subjects (HL+NL) revealed that age (p<0.001), sex (p<0.001), non-HDL-cholesterol (p<0.01) and BMI (p<0.05) were significant and independent predictors of IMT. CONCLUSIONS: The increase of IMT CCA in hyperlipidemic still clinically asymptomatic FCHL subjects corresponds to acceleration of the clinically ''silent'' atherosclerosis by about 8-14 years and is in agreement with their increased risk of atherosclerosis.

[Endothelial dysfunction in a family with familial combined hyperlipidemia]. / Endoteliální dysfunkce u clenu rodin s familiární kombinovanou hyperlipidémií.

Familial Combined Hyperlipidemia is the most frequent familial hyperlipidemia with a high risk a early manifestation of arteriosclerosis. Endothelial dysfunction is the first step in the development of arteriosclerosis. The aim of our investigation was to examine selected markers of endothelial dysfunction in hyperlipidemic members of families with familial combined hyperlipidemia and their normolipidemia first-line relatives and to compare them with healthy individuals. The study includes non-smoking members of the affected families (probands and first-line relatives), who have not suffered from clinical manifestations of arteriosclerosis and/or hypertension during the start of the study. The cohort was divided into hyperlipidemic individuals (N = 25) and normolipidemic individuals (N = 21). Both groups were compared with control groups of healthy individuals (two groups, N = 17 each), who were adjusted by age and sex. The following markers of endothelial dysfunction were examined: 1. ultrasound--flow mediated dilatation of brachial artery and 2. humoral--serum levels of von Willebrand factor, inhibitor of activator of plasminogen-1 and vasoadhesive molecules (vascular cell adhesion molecule-1, intercellular adhesion molecule-1). The members of families with familial combined hyperlipidemia displayed symptoms of endothelial dysfunction. In comparison with healthy controls the endothelial dysfunction was more expressed in hyperlipidemic individuals. They displayed a significantly lower flow-mediated dilatation of brachial artery (3.6 +/- 3.3% versus 6.6 +/- 2.8%, P < 0.01), higher levels of von Willebrand factor (152.8% +/- 79.1% versus 110.4% +/- 24.8%, P < 0.05), inhibitor of activator of plasminogen-1 (94.6 +/- 30.8 ng/ml versus 60.4 +/- 38.0 ng/ml, P < 0.01) and vasoadhesive molecules: vascular cell adhesion molecule-1 (927.0 +/- 167.7 ng/ml versus 814.7 +/- 171.1 ng/ml, P < 0.05), intercellular adhesion molecule-1 (601.7 +/- 89.5 ng/ml versus 544.8 +/- 59.8 ng/ml, P < 0.05). The normolipidemic individuals displayed only a significantly lower flow-mediated dilatation of brachial artery (5.6 +/- 2.6% versus 7.5 +/- 2.8%, P < 0.05) and higher levels of von Willebrand factor (136.8 +/- 40.32% versus 104.1 +/- 24.9%, P < 0.05). No significant difference was found in the levels of inhibitor of activator of plasminogen-1 and vasoadhesive molecules. The results indicated that members of families with familial combined hyperlipidemia represent a high-risk group from the standpoint of early manifestation of arteriosclerosis.

[Ciprofibrate in the treatment of combined hyperlipoproteinemia. Results in more than 600 patients from 23 centers in the Czech Republic]. / Ciprofibrát v lécbe kombinované hyperlipoproteinémie. Výsledky u více nez 600 nemocných z 23 center v CR.

A total of 633 patients with combined hyperlipoproteinaemia from 23 centres in the Czech Republic met the criteria for assessment of the effectiveness of 3-month administration of 100 mg ciprofibrate (Lipanor) per day. The cholesterol concentration declined from the original values of 6.94 mmol/l by 13%. The drop of triglycerides was even more significant from 3.03 mmol/l by more than 41%. The relatively low HDL cholesterol at the beginning, 1.14 mmol/l, increased by 15%, while LDL-cholesterol dropped significantly by almost 12%. The classical atherogenic index expressed by the ratio of total/HDL cholesterol declined by 25%. Treatment was very well tolerated by the patients and was associated with a minimum of undesirable side-effects. Treatment with ciprofibrate is effective and safe treatment in patients with combined hyperlipoproteinaemia.

[Dyslipoproteinemia and diabetes mellitus]. / Dyslipoproteinémie a diabetes mellitus.

Diabetes mellitus is, as compared with the non-diabetic population, associated with a much higher mortality of ischaemic heart disease and other cardiovascular diseases. In this risk participates in a major way also diabetic dylipidaemia. The latter is characterized in particular by hypertriglyceridemia which reflects the increase of VLDL and IDL lipoproteins. Elevated and prolonged postprandial lipaemia participates in the development of qualitative lipoprotein changes. Highly athergenic "small dense LDL" are formed which are liable to an oxidative modification and are then in an unregulated manner taken up in the vascular wall. Reduction of HDL-cholesterol and a change in the different HDL sub-populations leads then to a deteriorated reverse cholesterol transport. Type 2 diabetes mellitus is associated with dyslipidaemia in the majority of patients even under conditions of satisfactory compensation of diabetes, in particular during the postprandial stage. On the other hand, in type 1 diabetes the lipid values usually become normal when the blood sugar level becomes normal, however qualitative changes of lipoproteins frequently persist. Increased glycation and oxidation of lipoproteins is a common sign of both types of diabetes. For prevention of cardiovascular complications treatment of diabetic dyslipidaemia is at least equally important as efforts to achieve optimal compensation of diabetes. Successful treatment of diabetic dyslipidaemia includes efforts to achieve compensation of diabetes, optimation of body weight, increase of physical activity, modification of diet, treatment of other secondary causes of hyperlipidaemia, and if these provisions are not successful, pharmacological hypolipidaemic treatment. The risk of macrovascular complications is so high in diabetics that according to recent knowledge it is not necessary to differentiate between primary and secondary prevention but aggressive treatment is necessary to achiebe target values of total cholesterol < 5.0 mmol/l and LDL-cholesterol < 3.0 mmol/l. Triglycerides > 2 mmol/l and HDL-cholesterol < 1 mmol/l are signs of a high cardiovascular risk. Optimation of the whole lipid profile is ideal.

[Dyslipoproteinemia and chronic kidney failure]. / Dyslipoproteinémie a chronické selhání ledvin.

Lipoprotein abnormalities are a regular part of metabolic changes associated with chronic renal failure. The character of dyslipoproteinaemia changes with the severity of disorders of renal functions, from initial deviations in the composition and distribution of circulating lipoprotein particles (a decline of glomerular filtration to 0.7-0.8 ml/s) to differently expressed changes of plasma lipid concentrations in terminal renal failure. The basis of the pathogenetic mechanism of these lipid abnormalities is the negative effect of the uraemic environment on the formation and catabolism of triglyceride-risk lipoproteins and on the function of the reverse cholesterol transport. An important part is also played by the modification of lipoprotein particles by oxidation and glycation. To a different extent also the nutritional status is manifested via the unfavourable composition of dietary fats, reduced effectiveness of antioxidant factors and in some instances also carnitine deficiency. Haemodialysis treatment and in particular peritoneal dialysis modify these lipid abnormalities. From the quantitative aspect renal dyslipoproteinaemia is not very striking, despite this its quantitative changes are important. It may have a negative impact on the progression of renal disease by its participation in the development of glomerular sclerosis and tubulointerstitial fibrosis. As one of the important risk factors it participates also in the acceleration of atherosclerosis in patients with chronic renal failure and in their much higher cardiovascular mortality as compared with the general population. These factors justify efforts to influence uraemic dyslipoproteinaemia. Fibrates or statins are indicated in conjunction with the supporting effect of diet and modification of the dialysis regimen. In tables and figures some results assembled by the authors are presented obtained in a group of dialyzed patients (characteristic of the lipid profile under basal conditions on fasting and after an oral lipid load and experience with influencing dysliopoproteinaemia by fenofibrates and atorvastatin).